Thursday, April 25th, 3-5pmCoffee and refreshments at 2:45pm; reception following the eventHarvard Medical School New Research Building – 77 Avenue Louis PasteurSeminar Room 1031

How do innovative medical technologies make their way to a global population, including patients in resource-limited settings? As centers of medical innovation, universities are well-placed to influence the global dissemination of the fruits of biomedical research and enhance access to advances in drug, vaccine, diagnostic and device technologies. In the past five years, several institutions in Boston and beyond have acknowledged this fact and taken bold steps to encourage the transfer of medical technologies to the developing world. Licensing provisions such as tiered, reduced and zero royalties for products sold in developing countries; march-in rights; agreements to agree; agreements not to patent or not to enforce patents in developing countries; and humanitarian licensing exceptions are just some of the strategies used to implement global access licensing of medical technologies. Others can be found in UAEM’s Global Access Licensing Framework, as well as the multi-institution Statement of Principles and Strategies for the Equitable Dissemination of Medical Technologies.

In this Forum, technology transfer officials and academic research leaders from Harvard, MIT, Tufts, BU, Northeastern, Children’s Hospital and Partners Healthcare (MGH/BWH) will speak to their institutions’ philosophy and experience with global access licensing strategies. In an hour-long Q&A, the audience – including invited experts with significant experience in medical technology development – will contribute to the discussion. The Forum is open to the public; and researchers, entrepreneurs, university leaders and students are highly encouraged to attend.

UAEM is an international interdisciplinary student organization that works with universities to leverage academic research for global health. Since our founding in 2001, we have worked towards illuminating the poorly understood process that brings discoveries from the laboratory to widely accessible products and services meant to improve human health.

Last week, Ryan Abbot blogged here about the Novartis case decided last Monday by the Supreme Court of India. Since then, there have been a broad range of reactions to the case, but many of them appear to have left a lurking elephant in the room.

I’d like to attempt to provide some clarity to a question that seems to have created a lot of confusion surrounding the impact of the Novartis decision: If the older alpha crystalline form of imatinib mesylate (generic Glivec) is already available in India, and the newer beta crystalline form is not more therapeutically efficacious, then why does it matter whether or not Novartis can get a patent on the newer version of Glivec? The simple answer is that for the most part, it doesn’t really, in terms of the availability of generic Glivec. At most, it may make a difference for some Indian patients who will do better with the beta crystalline form. And it will make some difference for Novartis, which will now forego a potential market of these Indian patients who would prefer to take (and can afford to pay for) the beta crystalline version. But the alpha crystalline form of imatinib mesylate was already available in generic form in India, and it would have continued to be available in generic form in India regardless of the outcome of this case. So why all the commotion?

First, the Novartis decision means that Indian generic manufacturers can now produce the beta crystalline form of imatinib mesylate with impunity. This means that Novartis is likely to face competition in its production of the beta crystalline form, over which it would otherwise have held a global monopoly. Indian generic manufacturers may now produce and export the beta crystalline form to other countries, which means that many more cancer patients in developing countries will have access to it. Novartis’s markets in these countries may be disrupted through parallel importation of cheaper generics.

As Jonathan Darrow notes below, on Monday, the Supreme Court heard oral arguments in Federal Trade Commission (FTC) v. Actavis, the “pay for delay” case questioning whether or not reverse payment settlements in Hatch-Waxman litigation should be presumptively anticompetitive, a question on which the Circuit Courts are divided. This particular case involves Solvay Chemicals Inc., whose patent on AndroGel cream, a synthetic testosterone formulation (set to expire in 2020) was challenged by three generic pharmaceutical companies that filed ANDA applications in 2003 for generic version of AndroGel (which is 1/6 the cost of the branded version). Following a 30-month stay triggered by Solvay’s subsequent infringement lawsuit, the FDA approved the generic version of Androgel in 2006, at which point the generic companies’ motion for summary judgment on the validity of Solvay’s patent was ready for decision. Instead of risking the judgment, the parties settled, with the generic companies agreeing to stay out of the market until 2015 in return for an estimated $186 – 252 million from Solvay over the course of six years. The FTC, expressing concern that consumers would ultimately bear the costs of delayed generic entry, unsuccessfully challenged this settlement as presumptively unlawful restraints of trade. The Eleventh Circuit affirmed the District Court’s decision in 2012, which rejected the FTC’s approach in favor of a “scope of the patent” test. Several months later, though, the Third Circuit reached the opposite verdict in a similar case, accepting the FTC’s position that reverse payment settlements are presumptively unlawful agreements not to compete. The Supreme Court granted cert to resolve this conflict.

I found a couple features of yesterday’s oral arguments particularly striking. First was Justice Breyer’s statement that he thought one of the four briefed scenarios in which a reverse payment settlement may rebut an anticompetitive presumption was “neutral”:

JUSTIC BREYER: [B]the person’s already in the market thinks that the next year or two or three years is worth $100 million a year, and the person who’s suing thinks it’s worth 30 million a year. And so he says, hey, I have a great idea, I’ll give him the 30 million and keep the 70. And — and that, I don’t see why that’s anticompetitive if that’s what’s going on.

Today, Professor Glenn Cohen announced on this blog that he, in conjunction with two others, filed an amicus brief in AMP v. USPTO (Myriad), a case concerning Myriad’s patents on isolated DNA and cDNA.In a paper I have been writing on the natural phenomenon doctrine as applied to biotechnology patents, I arrived at this conclusion about the doctrine’s implications for Myriad:

According to Mayo v. Prometheus, the preemption rationale for the natural phenomenon doctrine suggests that any patent on a diagnostic biotechnology product or process should be limited to the inventive use of that product or process as defined by its associated process or product, respectively. As applied to Myriad, this qualified interpretation of the natural phenomenon doctrine would suggest that ideally these patents ought to be limited to Myriad’s one remaining valid method claim, namely claim 20 of the ‘282 patent, “a method for screening potential cancer therapeutics.” The unavoidable and unsettling problem with such a conclusion, of course, is that at this stage in litigation, it is not possible for the Court to limit Myriad’s gene patents in this way. This procedural limitation sheds some light on the elephant in the natural phenomenon doctrine: If the doctrine was meant to exclude certain categories of discoveries from patentability before Congress had the opportunity to refine more specific patent validity rules, then perhaps it should be limited to carrying out that function at the outset of a patent prosecution. The natural phenomenon doctrine serves the important purpose of ensuring that patents do not contravene their Constitutional objective by too broadly preempting the use of “basic tools of science.” It does so by balancing the scope of preemption against the scope of invention, and ensuring that the scope of preemption does not exceed that which is justified by the inventor’s handiwork in applying natural phenomena. At the patent prosecution stage, the natural phenomenon doctrine is a useful “catch-all” analytical tool that allows flexibility in promoting the spirit of patent law when the letter of patent law has not kept pace with the progress of science. But at the litigation stage, its Achilles heel is that it may prove too much: In the absence of a procedural option to limit a patent at this stage, the natural phenomenon doctrine is forced to err on either the side of all or nothing. While the doctrine may be useful at the patent prosecution stage, it was not (as other statutory patentability requirements were) appropriately designed to assess the validity of patents once they’ve been issued in a way that is compatible with today’s patent litigation procedures. As a doctrine of limitation, it must in this context either fall, and prove nothing at the expense of unwarranted preemption, or rise, and prove too much at the expense of patent holders who have been reasonably relying on guidance from the USPTO regarding gene patents for many years.

I am unable to find any commentary exactly on this point, but some issues concerning the jurisdictional authority of §101 have been raised in response to both Mayo and CLS Bank v. Alice. While these cases concern biotechnology processes and software, respectively, they are extremely relevant to Myriad if we consider isolated genes / cDNA to be the equivalent of biological software. Indeed, Professor Ronald Mann observed that “Though most of the attention to …[Mayo] has focused on its immediate implications for medical providers, the broader effect of the case probably will be on the software industry.”

I. Fundamentals: the background of health policy and medical technology, the work of the three organizations, the burden of disease that challenges health policy, and the factors shaping that policy. Much attention has been paid to diseases such as HIV/AIDS, malaria and tuberculosis, but noncommunicable diseases such as cancer, diabetes and heart diseases are a rising challenge.II. The Policy Context: the international framework, linking health policy, intellectual property and trade, the contributions of economic analysis, and the use of traditional medical knowledge in research.III. Innovation in Greater Detail: the evolution of research and development, alternative ways of promoting innovation for neglected diseases, the role of intellectual property rights, with examples.IV. Access: how to ensure pharmaceuticals and other medical technology reach the people who need them: pricing policies, taxes and import duties, procurement, regulation, technology transfer, local production, patents, compulsory and voluntary licences, trade agreements, and competition policies, etc.

In her remarks at the launch of the publication, WHO Director-General Dr. Margaret Chan emphasized the importance of the public interest not only in public health, but also intellectual property and trade policy. Importantly, Dr. Chan noted that it “is worth considering” an extension of the TRIPS Agreement (WTO Agreement on Trade-Related Aspects of Intellectual Property) transition deadline (currently set to July 1, 2013) for least-developed countries (LDCs) to implement the agreement’s provisions.

In stark contrast, last week the Journal of Economic Perspectives released an empirical study by two Federal Reserve economists calling for the abolition of the patent system. Continue reading →

In December, I wrote a blog post noting that access to biomedical research is critical not only for informed patient care, but also for the sustainable development of pharmaceutical R&D responsive to local needs, especially in developing countries. In recent years, open access issues have taken on an increasingly important role in global health discussions. In 2009, the Institute for Information Law and Policy, the Justice Action Center and Health Information for All 2015 made the case for a rights-based approach to the issue in a report called Access to Health Information under International Human Rights Law. In 2011, a medical student in the Right to Research Coalition explained 6 Reasons Open Access Matters to the Medical Community. And the 2012 WHO CEWG Report recommending a binding treaty on Research and Development to Meet the Needs of Developing Countries includes as one of its proposals “open approaches to research and development and innovation which include precompetitive research and development platforms, open source and open access schemes.”

In response to the increasing demand for open access to biomedical research, PLOS Medicine partnered with WHO to issue a call for papers “intended to culminate in an open-access collection of original research and commentary articles to coincide with the launch … [of] World Health Report 2012: No Health without Research.” However, the 2012 World Health Report was unexpectedly called off to be replaced by a 2013 report on “contributions to research to universal health coverage,” a far less politically polarizing topic. In its editorial response to the cancellation of the 2012 Report, PLOS Medicine noted that “The reasons for these delays and for the changes in scope of WHO’s flagship publication, are unclear,” not in the least because “Previous World Health Reports … have represented bold political statements.”

In a couple days, petitioners in AMP v. USPTOwill be filing their brief on the merits following the Supreme Court’s grant of certiorari in late November. For many, the Supreme Court’s ruling in this case will provide a long-awaited answer to the question of whether or not isolated DNA is patentable subject matter under §101. In August, the Federal Circuit ruled on the case for a second time following a remand from the Supreme Court, in which the Federal Circuit was asked to reconsider its ruling in light of the Supreme Court’s recent ruling in Mayo v. Prometheus. The majority, written by Judge Lourie, found that Mayo did “not control the question of patent-eligibility of such claims. They are claims to compositions of matter” and that while “Plaintiffs and certain amici state, that the composition claims are mere reflections of a law of nature. Respectfully, they are not, any more than any product of man reflects and is consistent with a law of nature.” Judge Bryson’s dissent, on the other hand, explained that, “In cases such as this one, in which the applicant claims a composition of matter that is nearly identical to a product of nature, it is appropriate to ask whether the applicant has done ‘enough’ to distinguish his alleged invention from the similar product of nature,” concluding that Myriad had not made a “substantial ‘inventive’ contribution” or claimed anything more than a combination of “well-understood, routine, conventional” elements.”

It seems likely that the Supreme Court will agree with Judge Lourie that the gene patents in question in Myriad, whether or not they are products of nature,are not laws of nature, as some of the patents in question in Mayo were. Yet I would be surprised if they took this to mean that Mayo therefore does not control the question of patent-eligibility in Myriad. In Mayo, Justice Breyer’s majority opinion was incredibly clear that the metabolic correlation at issue was not patentable under §101 because it tied up a law of nature and therefore preempted its use for further research. Isn’t that exactly what Myriad is about? Certainly all parties would agree that Myriad’s patents, whether natural products (physical phenomena) or not, serve to preempt breast cancer research on the BRCA1 and BRCA2 genes.

When the Supreme Court articulated the §101 exception for laws of nature, physical phenomena and abstract ideas in Gottschalk v. Benson, it explained that these kinds of claims were not patentable because they consist of the “basic tools of scientific and technological work.” It is difficult to dispute that Myriad’s isolated genes are basic scientific tools. But according to Myriad, under this rule, their patents would only be invalid if they claimed real human DNA, and that it is not dispositive that their isolated DNA is nearly identical to real human DNA, because it is not naturally occurring.

The 2012 Global Congress on Intellectual Property and the Public Interest has just come to a close in Rio de Janeiro, Brazil. The conference brought together global leaders in intellectual property-related fields like access to medicines, access to knowledge, internet freedom, innovation and development, and open educational resources. I was invited to participate in the various sessions concerning access to medicines, which focused on two sides of this global health challenge.

The first part of the access discussions focused on best practices and threats in the use of TRIPS flexibilities in developing countries. Participants emphasized the need to look beyond the usual focus on compulsory licenses to set new priorities for understanding and leveraging less-developed flexibilities such as patentability criteria, patent opposition mechanisms and parallel importation. An important overarching theme in these discussions was reframing flexibilities as rights, as they carry the same legal status as the intellectual property rights which make them necessary.

The other side of the discussions focused on innovation and research and development (R&D) for the developing world, primarily through recent advances by the WHO CEWG report in promoting a binding convention in this realm. At the forefront of these proposals is the notion that incentives for innovation should be de-linked from product prices in order to address the needs of the developing world. Participants emphasized that, moving forward, advocates should be careful to ensure that public and institutional debates on alternative R&D models do not narrow their focus from neglected populations to neglected diseases.

As of 2008, the NIH Public Access Policy requires “that all investigators funded by the NIH submit or have submitted for them to the National Library of Medicine’s PubMed Central an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication.” Four years later, approximately 80% of NIH-funded research articles make their way into PubMed Central. Institutional Open Access resolutions such as Harvard’s Open Access Policy have helped accommodate the NIH Public Access Policy requirements, but Harvard Medical School and Harvard School of Public Health have yet to adopt it.

In May, the Harvard Library Faculty Advisory Council issued a public letter calling on faculty to promote open access scholarly publishing, noting that “Many large journal publishers have made the scholarly communication environment fiscally unsustainable and academically restrictive”. In a Petrie-Flom Center-sponsored Open Access Week panel (moderated by Open Access LiaisonsScott Lapinski and June Casey), Peter Suber, Amy Brand, Winston Hide and Patrick Taylor discussed the challenges and opportunities for progress towards achieving open access to health research. Highlights from the panel are presented below, and the video should be available on the Petrie-Flom website shortly.

Earlier this year, the World Health Organization’s Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG) issued a report calling for, inter alia, increased support for innovative pharmaceutical R&D funding mechanisms. Although lack of financing has posed a challenge to implementation of alternative approaches to R&D, the increasing pace of pharmaceutical innovation has certainly spurred significant innovation in this realm. These approaches can be broadly categorized into “push” and “pull” incentive mechanisms.

Last week, Public Citizen published a Health GAP analysis entitled “Leaked TPP Investment Chapter Presents a Grave Threat to Access to Medicines,” in which Professor Brook Baker explains four ways in which access to medicines is compromised by the USTR’s leaked investment chapter proposal for the Trans-Pacific Partnership Agreement. The problematic provisions he identifies — inclusion of intellectual property (IP) in the definition of “investment”, ambiguous scope of minimum standards of treatment, inadequate exceptions and limitations for public interest measures, and performance requirement limitations preventing development of local and sustainable production—are not new, but have been included either implicitly or explicitly in countless bilateral investment treaties (BITs) (including the U.S. Model BIT) and the investment chapters of free trade agreements (FTAs) (including virtually all US FTAs and the proposed EU-India FTA). Such inclusion gives more “teeth” to foreign investors’ IP rights, but what of access to medicines?

The 14th round of negotiations for the Trans-Pacific Partnership Agreement (TPPA, a multilateral trade agreement currently being negotiated by the USTR and 10 other countries) is currently underway in Leesburg, VA. Last month, KEI posted a brief video blog about an interesting provision (Article 8.2) of the TTPA’s leaked draft IP chapter calling for patentability of diagnostic, therapeutic and surgical methods. Critically, KEI pointed out that current US law (35 U.S.C. 287(c))—which was amended after widespread concern from physicians’ associations regarding the adverse public health effects of medical method patent liability were brought to light with Pallin v. Singer, 36 U.S.P.Q.2d (BNA) 1050 (D. Vt. 1995)—immunizes medical practitioners from patent infringement suits concerning medical methods, although the draft TPPA provision makes no such exception. The proposed provision is also contrary to Article 27(3) of TRIPS and Article 1709(3)(a) of NAFTA, all of which allow countries to exclude such medical methods from patentability, as well as Rule 39.1 of the 1970 PCT, which exempts International Searching Authorities from having to conduct patent searches relating to medical methods.

Medical professional societies, including the WMA, AMA, AAOS, ACOG and ASRC, have also opposed medical procedure patents on ethical grounds. The WMA has explained that patents are not necessary to incentivize innovation in medical procedures: “Unlike device development, which requires investment in engineers, production processes, and factories, development of medical procedures consists of physicians attaining and perfecting manual and intellectual skills… physicians already have both obligations to engage in these professional activities as well as rewards for doing so.” The WMA has also noted a number of adverse effects on access to medical care resulting from medical procedure patents, including higher costs, fewer physicians available and/or willing to perform patented procedure, and less innovation in medical procedures.